Cadmium Decreases SGLT1 Messenger RNA in Mouse Kidney Cells

Blumenthal, Samuel S.; Ren, Lifen; Lewand, Donna L.; Krezoski, Susan; Petering, David H.

doi:10.1006/taap.1997.8353

Cited by 15 publications

(14 citation statements)

References 31 publications

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“…up to 24 h and studied the expression of one of the apical Na ? -glucose cotransporters, SGLT1 (Blumenthal et al 1998). Within 12 h, the relative concentration of SGLT1 mRNA decreased, resulting in a decreased synthesis and steady state level of the Na ?…”

Section: Cadmium Effects On Membrane Transport Of Glucose and Amino Amentioning

confidence: 99%

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Cadmium and transport of ions and substances across cell membranes and epithelia

2010

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Toxic metals such as cadmium (Cd(2+)) pose serious risks to human health. However, even though the importance of Cd(2+) as environmental health hazards is now widely appreciated, the specific mechanisms by which it produces its adverse effects have yet to be fully elucidated. Cd(2+) is known to enter cells, it binds and interacts with a multitude of molecules, it may indirectly induce oxidative stress and interfere with gene expression and repair of DNA. It also interacts with transport across cell membranes and epithelia and may therefore disturb the cell's homeostasis and function. Interaction with epithelial transport, especially in the kidney and the liver, may have serious consequences in general health. A lot of research still needs to be done to understand the exact way in which Cd(2+) interferes with these transport phenomena. It is not always clear whether Cd(2+) has primary or secondary effects on cell membrane transport. In the present review we try to summarize the work that has been done up to now and to critically discuss the relevance of the experimental work in vitro with respect to the in vivo situation.

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Section: Cadmium Effects On Membrane Transport Of Glucose and Amino Amentioning

confidence: 99%

“…on the expression of the Na ? -glucose cotransporter (Blumenthal et al 1998). Curiously enough, effects of Cd 2?…”

Section: Cadmium Effects On Membrane Transport Of Glucose and Amino Amentioning

confidence: 99%

Cadmium and transport of ions and substances across cell membranes and epithelia

2010

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“…This decline in glucose uptake accompanied decreases in mRNA levels of both SGLT1 and SGLT2 (Blumenthal et al, 1998; Tabatabai et al, 2001). The reduced mRNA level of SGLT1 in Cd-exposed kidney cells resulted from a transcriptional effect and did not involve enhanced mRNA degradation (Tabatabai et al, 2005).…”

Section: Introductionmentioning

confidence: 93%

Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: Possible reaction of cadmium with the zinc finger domain of Sp1

Kothinti

Blodgett

Petering

et al. 2010

Toxicology and Applied Pharmacology

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Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose transporters, SGLT1 and SGLT2 and that Sp1 from Cd-exposed cells displayed reduced binding to the GC boxes of the mouse SGLT1 promoter in vitro. Here, we identified a GC box upstream of mouse SGLT2 gene. ChIP assays on PMKC revealed that exposure to 5 μM Cd abolished Sp1 binding to SGLT1 GC box while it decreased Sp1 binding to SGLT2 GC sequence by 30% in vivo. The in vitro DNA binding assay, EMSA, demonstrated that binding of Sp1 from Cd (7.5 μM)-treated PMKC to the SGLT2 GC probe was 86% lower than in untreated cells. Sp1 is a zinc finger protein. Compared to PMKC exposed to 5 μM Cd alone, inclusion of 5 μM Zn restored SGLT1 and 2 mRNA levels by 15% and 30%, respectively. Cd (10 μM) decreased the binding of recombinant Sp1 (rhSp1) to SGLT1 and SGLT2 GC probes to 12% and 8% of untreated controls. Cd exerted no effect on GCbound rhSp1. Co-treatment with Cd and Zn showed that added Zn significantly restored rhSp1 binding to the SGLT1 and SGLT2. Addition of Zn post Cd treatment was not stimulatory. We conclude Cd can replace Zn in Sp1 DNA binding domain to reduce its binding to GC sites in mouse SGLT1 and SGLT2 promoters.

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“…In one study adipocytes isolated from rats previously exposed to Cd had reduced glucose transport activity that was associated with decreased expression of the glucose transporter (GLUT4) [13]. In another study, primary mouse renal cortical cells exposed to Cd in vitro showed a decrease in both glucose uptake and expression of SGLT1, a Na + -dependent glucose symporter [37]. Further studies are needed to sort out the roles of these various organs and their interrelationships in mediating the actions of Cd on glucose transport.…”

Section: Mechanims Of Cadmium-mediated Hyperglycemia / T2dmmentioning

confidence: 99%

A Review of Diabetes Mellitus and Exposure to the Environmental Toxicant Cadmium with an Emphasis on Likely Mechanisms of Action

Edwards

Ackerman²

2016

CDR

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There is increasing interest in how exposure to environmental substances can contribute to the onset of Type II diabetes mellitus (T2DM). Impaired insulin release is a hallmark of type I diabetes mellitus and is involved in the progression of T2DM. Both epidemiological and experimental studies show that exposure to the environmental pollutant cadmium (Cd), is associated with hyperglycemia, T2DM and reduced serum insulin. The goal of this review is to examine likely mechanisms of action of Cd-induced dysglycemia based on experimental studies in the literature and from the most recent findings in the Edwards lab. The primary focus of this review will examine how Cd may cause islet dysfunction and subsequent impaired insulin release. Recent findings in the Edwards lab indicate that Cd causes time-dependent and statistically significant changes in fasting leptin, Glucose-dependent Insulinotropic Polypeptide (GIP) and pancreas polypeptide hormone levels in a subchronic animal model of Cd-induced hyperglycemia. This review summarizes the most likely cellular mechanisms by which the ubiquitous environmental contaminant Cd disrupts glucose homeostasis. While individual cellular effects of Cd are reviewed it is likely that no one single mechanism is involved, rather multiple mechanisms exist and work synergistically resulting in islet dysfunction and ultimately dysglycemia.

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Cadmium Decreases SGLT1 Messenger RNA in Mouse Kidney Cells

Cited by 15 publications

References 31 publications

Cadmium and transport of ions and substances across cell membranes and epithelia

Cadmium and transport of ions and substances across cell membranes and epithelia

Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: Possible reaction of cadmium with the zinc finger domain of Sp1

A Review of Diabetes Mellitus and Exposure to the Environmental Toxicant Cadmium with an Emphasis on Likely Mechanisms of Action

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